title: Clinical relevance of cancer stem cells in bone marrow of early breast cancer patients.
abstract: BACKGROUND
  Cancer stem cells (CSCs) are epithelial tumor cells that express CD44(+)CD24(-/lo). CSCs can be further divided into those that have aldehyde dehydrogenase (ALDH) activity (Aldefluor(+)) and those that do not. We hypothesized that if CSCs are responsible for tumor dissemination, their presence in bone marrow (BM) would be prognostic in early stages of breast cancer (EBC) patients.
  
  
  METHODS
  BM aspirates were collected at the time of surgery from 108 patients with EBC. BM was analyzed for CSCs and ALDH activity by flow cytometry. Overall survival and disease-free survival (DFS) were calculated from the date of diagnosis and analyzed with Kaplan-Meier survival plots. Cox multivariate proportional hazards model was also carried out.
  
  
  RESULTS
  Patients with CSCs in BM had a hazard ratio (HR) of 8.8 for DFS (P = 0.002); patients with Aldefluor(+) CSCs had a HR of 5.9 (P = 0.052) for DFS. All deceased patients (n = 7) had CSCs in BM. In multivariate analysis, the presence of CSCs in BM was a prognostic factor of DFS (HR = 15.8, P = 0.017).
  
  
  CONCLUSIONS
  The presence of BM metastasis is correlated with CSCs and these CSCs irrespective of ALDH activity are an independent adverse prognostic factor in EBC patients.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Endocrinology and Molecular and Clinical Oncology, University of Naples Federico II, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: H
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Cohen
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: S
authors.initials: S
authors.lastname: Anfossi
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: J
authors.initials: J
authors.lastname: Khoury
authors.affiliation: Departments of Biostatistics.
authors.forename: K
authors.initials: K
authors.lastname: Hess
authors.affiliation: Pathology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: S
authors.initials: S
authors.lastname: Krishnamurthy
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tin
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia.
authors.forename: M
authors.initials: M
authors.lastname: Cristofanilli
authors.affiliation: Departments of Breast Medical Oncology.
authors.forename: G N
authors.initials: GN
authors.lastname: Hortobagyi
authors.affiliation: Radiation Oncology.
authors.forename: W A
authors.initials: WA
authors.lastname: Woodward
authors.affiliation: Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lucci
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: jreuben@mdanderson.org.
authors.forename: J M
authors.initials: JM
authors.lastname: Reuben
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000032:analysis / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000473:pathology; D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology*; D051927:CD24 Antigen / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D051927:CD24 Antigen; D018960:Hyaluronan Receptors; D000444:Aldehyde Dehydrogenase
keywords: CD24; CD44; bone marrow; breast cancer; cancer stem cells; circulating tumor cells